| Classically, IBD (especially in CD) is associated with a hyperactive innate immune response |
| producing unrestrained levels of proinflammatory cytokines and chemokines (e.g., IL-12, IFN- |
| γ, and TNF-α), resulting in a marked expansion of lamina propria. This propagates further |
| inflammation by recruiting T-helper 1 (CD4+ Th1) cells. Alternatively, the opposite scenario can |
| occur in which resident tissue macrophages fail in their attempt to initiate an innate immune |
| response against foreign antigens and are defective in the secretion of proinflammatory |
| cytokines [42, 43]. Reduced concentrations of these mediators mean neutrophil recruitment |
| cannot be adequately enforced at the lamina propria, resulting in impaired clearance of antigenic |
| contents [44]. The following overcompensatory immune responses lead to either a polarization |
| toward an atypical humoral phenotype driven by T-helper 2 (CD4+ Th2) cells along with |
| mediators such as IL-4 and IL-13 (especially in UC [45]) or recruitment of CD4+ Th1 cells |
| [36]. The amplification of inflammatory response as an attempt to remove foreign material only |
| incites further epithelial injury which coincides with a decreased production of defensins [46, 47]. |
| It is quite possible that both paradigms may be true given the genetic heterogeneity among |
| IBD populations. A newly discovered subset of inflammatory T cells, known as T-helper 17 |
| (Th17) cells, produces the proinflammatory cytokine IL-17 and requires IL-23 for proper |
| maintenance and function. Indirectly, Th17 cells relate CD and UC etiologies due to IL-23 |
| sharing similar subunits with another major cytokine found in the Th1 phenotype, namely, IL-12 |
| [48, 49]. Also, responsiveness to anti-TNF-α treatment suggests common pathogenic pathways |
| are shared by both IBD subtypes [50, 51]. |
